Quinolines are prevalent in natural product chemistry, and are important building blocks in organic synthesis, drug discovery and materials science. Owing to their importance, various named reactions are used, including Combes quinolines synthesis, Conrad-Limpach synthesis, Doebner-Miller reaction, Friedlander synthesis, Povarov reaction, Camps quinolines synthesis, Knorr quinolines synthesis and Gould-Jacobs reaction. However, most of these reactions involve strong acid, toxic chemicals (nitrobenzene and iodine) and high temperature reactions, even though they lead to low yields. Although the use of an iridium catalyst might circumvent this problem, this homogeneous catalyst is difficult to recover and recycle. The high cost of iridium metal might also detract from its use. Thus, there is an urgent need to develop a recyclable catalytic system, preferably that uses non-toxic reagents in the synthetic reactions.
U.S. Pat. No. 6,103,904 (Eva) discusses iodide and iodide salts (such as sodium and potassium iodide) to synthesize quinolones. These catalysts apepar to require high pressure and temperature and use of toxic oxidizing agents including nitroaromatics and arsenic compounds. U.S. Pat. No. 5,700,942 (McAteer) discusses a process for preparing quinoline bases using non-metal catalysts including amorphous silica-alumina or zeolite. The reactions occur in vapor phase, and appear to require high temperature (400 to 550° C.). U.S. Pat. No. 4,617,395 (Dockner) relates to preparation of quinolines, but requires high boiling mineral oil (b.p. above 150° C.), and use a non-metal organic acid as a catalyst. The aldehydes useful in the method appear limited to α, β-monosaturated aldehyde, and require stoichiometric amounts of an oxidant which may be toxic, such as nitrobenzene, arsenic pentoxide, or iron (II) chloride.
Other more recent approaches to quinoline synthesis have included iridium complexes T. Igarishi, et al., Chem. Lett. 2005, 34, 106-07; T. Nakajima, et al., Bull. Chem. Soc. Jan. 2006, 79, 1941-49), or acid catalyzed synthesis of anilines with aldehydes to quinolines (S.-Y. Taualea, J. Org. Chem. 2006, 71, 800-03.). For general reviews on the synthesis of quinolines see Li, J. J. (ed.), Name Reactions in Heterocyclic Chemistry, Wiley-Interscience, Hoboken, N.J., 2005, pp. 35-494; J. A. Joule K. Mills Heterocyclic Chemistry, Wiley-Blackwell Oxford, 2010, pp. 188-198. The foregoing references are incorporated herein by reference. M. Sainsbury, Heterocyclic Chemistry, Royal Soc. Chem., Cambridge 2001, pp. 43-50; R. F. Manske, Chem. Rev. 1942, 30, 113-14. The foregoing methods involve strenuous reaction conditions, toxic reactants, low yields, environmentally unfriendly methods, catalysts, or reactants, or a combination of the foregoing.